title: Regulation of NK92-MI cell cytotoxicity by substance P.
abstract: The neuropeptide substance P (SP) can regulate a number of immunological functions in vitro and in vivo and may regulate natural killer (NK) cell activity. Here, we investigated whether SP has a role in regulating NK92-MI cell function in vitro, and how it influences NK cell activity. We found that SP dose dependently increased the cytotoxicity of NK92-MI cells and had a maximal effect at a concentration of 10(-12) and 10(-10) m. Furthermore, the expression of cytotoxic-associated molecules (perforin, granzyme) and activating receptor NKp46 [a member of natural cytotoxicity receptors (NCRs)] was observed to be upregulated by SP at optimal concentration, at which SP enhanced the cytotoxicity of NK92-MI cells. Neurokinin-1 receptor (NK-1R), a functional receptor of SP, was found on NK92-MI cells, and the observed effects of SP on NK92-MI cells could be more partially blocked by an NK-1R antagonist. Our data suggest that SP induces NK92-MI cell cytotoxicity by directly increasing the expression of cytotoxic granules and upregulates NK92-MI cell receptor-mediated functions indirectly. Thus, SP may regulate NK cell function mainly through NK-1R.
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China.
authors.forename: W X
authors.initials: WX
authors.lastname: Fu
authors.forename: B
authors.initials: B
authors.lastname: Qin
authors.forename: A P
authors.initials: AP
authors.lastname: Zhou
authors.forename: Q Y
authors.initials: QY
authors.lastname: Yu
authors.forename: Q J
authors.initials: QJ
authors.lastname: Huang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Liang
mesh_terms: D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000096:biosynthesis / Q000276:immunology; D064729:Neurokinin-1 Receptor Antagonists; D054353:Perforin / Q000096:biosynthesis / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000276:immunology; D013373:Substance P / Q000276:immunology* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D054353:Perforin; D013373:Substance P; D053804:Granzymes